Malarial disease represents one of the most pressing medical healthcare issues facing the world today. While limited drug treatment options exist, a vaccine solution is widely considered as one of the most effective therapeutic weapons to combat malaria. Despite years of research, though, malarial vaccine initiatives have yet to produce a viable candidate. One vaccine candidate continues to show potential: the anti-toxin malaria vaccine. This approach directs the immune response against the carbohydrate portion of the malaria toxin, glycophosphotidyl inositol (GPI), a glycolipid. Given the significant advances in GPI carbohydrate synthesis supported by a Phase I SBIR, a drug development path for the malarial GPI vaccine candidate can now be proposed and executed. To develop the vaccine candidate the following objectives will be addressed: 1. Synthesis and characterization of multigram quantities of GPI antigen molecule. This will be performed utilizing the protocols developed during the Phase I SBIR. 2. Preliminary efficacy and safety studies. The vaccine candidate will be evaluated for efficacy in a rodent model of cerebral malaria and in two species safety. 3. Establishment of analytical and synthesis processes to enable drug substance generation. The synthesis process will be optimized and analytical methods will be developed to facilitate reliable, large-scale vaccine generation 4. Efficacy evaluation in a primate model. Vaccine candidates will be tested in a primate malarial model system for their ability to prevent cytokine cascade and anemia. 5. Pre-Good Laboratory Practices (GLP) drug substance evaluation. The drug substance and synthetic process will be characterized fully. Multigram pilot batches of material will be produced and analyzed The goal is to establish the final process development path that will generate the formal data and protocols required to enable an investigational new drug (IND) application for the malarial GPI vaccine candidate. ? ?
